Our studies have concerned regulation of gene expression during normal and abnormal differentiation processes. Hybridization, S1 mapping, and primer extension experiments demonstrated that the 2.2-kb and 1.7kb AFP mRNAs contain identical sequences from the eighth (G) exon to the 3' end of the 2.2-kb RNA but differ in sequences at the 5' end. The 1.7-kb RNA lacks sequence of the seven 5' exons present in the 2.2 kb RNA. However, this variant RNA contains additional sequences 5' to the G exon. The ts rat fetal hepatocytes grown at 40 degree C matured into the adult hepatocytes in the presence of glucocorticoid hormones. This was demonstrated by the inhibition of fetal gene but induction of adult gene expression by glucocorticoids. We have also demonstrated that adult liver produced an AFP mRNA which is indistinguishable from the 1.7 kb AFP mRNA. Glucocorticoids stimulated synthesis of the variant AFP encoded by the 1.7 kb RNA but did not enhance production of the corresponding mRNA. Expression of tyrosine amino transferase (TAT) gene in the ts adult hepatocyte line was ts and dependent upon the presence of glucocorticoid. cAMP alone was not sufficient to induce TAT gene expression, but it enhanced the induction by the steroid hormone. cDNAs encoding human placental pregnancy-specific beta1- glycoprotein (PSbetaG) have been isolated and characterized. Two cDNA clones (PSG16 and PSG93) differ only in sequence in the 3' end of the coding region. PSG93 contains an additional 86 bp at the end of the 3' coding region of PSG16. This insertion results in the generation of PSbetaG species of 418 amino acid residues instead of the 416 amino acid residues predicted by PSG16. These cDNA probes were used to study regulation of PSbetaG gene expression in human placental fibroblasts. We found that the PSbetaG synthesized by the fibroblasts was structurally different from placental PSbetaG.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C et al. (2018) Hepatic glucose-6-phosphatase-? deficiency leads to metabolic reprogramming in glycogen storage disease type Ia. Biochem Biophys Res Commun 498:925-931
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Walker, Elizabeth A; Ahmed, Adeeba; Lavery, Gareth G et al. (2007) 11beta-Hydroxysteroid Dehydrogenase Type 1 Regulation by Intracellular Glucose 6-Phosphate Provides Evidence for a Novel Link between Glucose Metabolism and Hypothalamo-Pituitary-Adrenal Axis Function. J Biol Chem 282:27030-6
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Cheung, Yuk Yin; Kim, So Youn; Yiu, Wai Han et al. (2007) Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta. J Clin Invest 117:784-93
Chou, Janice Y; Mansfield, Brian C (2007) Gene therapy for type I glycogen storage diseases. Curr Gene Ther 7:79-88
Ghosh, A; Allamarvdasht, M; Pan, C-J et al. (2006) Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer. Gene Ther 13:321-9
Nguyen, Andrew D; Pan, Chi-Jiunn; Weinstein, David A et al. (2006) Increased scavenger receptor class B type I-mediated cellular cholesterol efflux and antioxidant capacity in the sera of glycogen storage disease type Ia patients. Mol Genet Metab 89:233-8
Kim, So Youn; Nguyen, Andrew D; Gao, Ji-Liang et al. (2006) Bone marrow-derived cells require a functional glucose 6-phosphate transporter for normal myeloid functions. J Biol Chem 281:28794-801
Shieh, J-J; Pan, C-J; Mansfield, B C et al. (2005) In islet-specific glucose-6-phosphatase-related protein, the beta cell antigenic sequence that is targeted in diabetes is not responsible for the loss of phosphohydrolase activity. Diabetologia 48:1851-9

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